Background/Aim: Low-dose aspirin therapy (1 × 75–150 mg) is used in the secondary prevention of cardiovascular diseases. Recently it has been suggested that a twice daily regimen is more effective (2 × 40–75 mg). We therefore compared the precision of four subdivision methods. Method: A total of 280 aspirin tablets (acetylsalicylic acid 80 mg) were subdivided using four different methods (PillTool, hand, knife and Pilomat). Precision was compared using a difference score and loss of mass. The accuracy (uniformity of weight) was evaluated according to an adapted version of the European Pharmacopoeia test. Loss of mass was analysed using the criteria of the US Food and Drug Administration. Results: Evaluating the difference score (mean ± SD: PillTool 22 ± 14; hand 14 ± 8; knife 36 ± 23; and Pilomat 20 ± 13), the knife method was less precise than the PillTool, the hand method and the Pilomat (for all p < 0.001). Furthermore, the hand (p < 0.001) and the PillTool (p < 0.001) had statistically significantly a smaller loss of mass (mg) than the knife and the Pilomat (median (interquartile range): PillTool 1 (2), hand 0 (2), knife 4 (6) and Pilomat 3 (5)). Only breaking by hand complied with the adapted European Pharmacopoeia test. Tablets broken by PillTool and hand fulfilled the criteria of the US Food and Drug Administration test for loss of mass. Conclusion: Based on the results of our study, we recommend hand breaking and to avoid a knife for the best weight uniform tablets. If a tablet splitting device is necessary we advise use of the PillTool.